Individuals with spinal cord injuries (SCl) above T6 experience episodic bouts of life-threatening hypertension termed autonomic dysreflexia (AD). If not treated promptly, the hypertension may produce cerebral and sub-arachnoid hemorrhage, seizures, ventricular arrhythmias, renal failure, and may lead to death. Enhanced vasoconstrictor responses to sympathetic stimulation may account for some, if not the majority, of the pressor response of AD. Sympathetic stimulation causes vasoconstriction by co-releasing norepinephrine onto alpha-adrenergic receptors, neuropeptide Y (NPY) onto Y1 receptors and ATP onto P2x purinoreceptors. To date, only the role of alpha-adrenergic receptor hyper-responsiveness in mediating AD has been investigated. This is surprising since it is well documented that the pattern of sympathetic nerve activity determines the relative contribution that each co-transmitter makes to vasoconstriction. Importantly, SCI alters the pattern of sympathetic activity. Furthermore, the influence of SCI on endothelium-dependent vasodilation and buffering of sympathetically mediated vasoconstriction has not been investigated. Importantly, endothelial derived nitric oxide and vasodilatory prostacyclin buffers the vasoconstrictor response to sympathetic stimulation. Finally, measures designed to reduce vasoconstrictor hyper-responsiveness have not been examined. A single bout of dynamic exercise attenuates the post-exercise vasoconstrictor response to sympathetic stimulation. Thus, the ability of vessels to respond to a change in sympathetic nerve activity after exercise is attenuated. Therefore, this proposal is designed to assess the role of sympathetic co-transmitters, endothelial function, and molecular adaptations on vasoconstrictor responses in intact and paraplegic rats. In addition, the effects of a single bout of exercise on vasoconstrictor responses will be examined. The clinical significance of the post-exercise modulation of vascular function will be determined by the evaluating the cardiovascular and sympathetic nerve responses to colon distension.